The synaptonemal complex protein Zip1 promotes bi-orientation of centromeres at meiosis I.
The synaptonemal complex protein Zip1 promotes bi-orientation of centromeres at meiosis I.
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DOI：
10.1371/journal.pgen.1000771
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发表时间：
2009-12
期刊：
影响因子：
4.5
通讯作者：
Dawson DS
中科院分区：
文献类型：
--
作者：
Gladstone MN;Obeso D;Chuong H;Dawson DS
在减数分裂I中，同源染色体配对，然后彼此分离到纺锤体的相反两极。在人类中，这一过程中的错误是导致出生缺陷、智力低下和不孕不育的主要原因。在大多数生物体中，同源伙伴之间的交换或交换提供了一种联系，促进了它们正确的、两极的对纺锤体的附着。在由主轴检查点触发的延迟期间，有时可以纠正两个伙伴连接到同一磁极的情况。对非交换染色体的研究表明，着丝粒配对是一种替代交换的方法，它通过定位着丝粒以实现适当的微管附着。在这里，我们展示了联会复合体蛋白ZIP1的一个新角色。ZIP1定位于粗线期非交换染色体的着丝粒上，介导着丝粒配对和减数分裂第一次配对时配对的分离。交换染色体的着丝粒配对也依赖于ZIP1。在联会复合体解体后，ZIP1被发现持续存在于着丝粒，直到微管附着。在纺锤体检查点突变体中，着丝粒配对的中断使交换染色体的分离随机化。这些结果表明，ZIP1介导的交换染色体着丝粒配对促进了微管的初始双极附着。ZIP1的这种活动减轻了纺锤体检查点的负荷，极大地降低了细胞因染色体对定向错误而退出检查点延迟的机会。因此，交换、纺锤体检查点和着丝粒配对是确保同源伙伴在减数分裂I中适当分离的补充机制。减数分裂是一种特殊的细胞分裂，它使染色体数量减半，并导致配子的产生。在人类中，减数分裂通常产生的配子恰好包含每个染色体的一个副本。减数分裂错误会导致配子的染色体数目不正确，这是导致出生缺陷和不育的主要原因。减数分裂(减数分裂I)的关键步骤是同源染色体的分离。同源染色体首先通过重组在物理上联系在一起，这使它们保持在一起，直到它们在着丝粒上正确地附着在将它们拉到细胞两端的装置上。在这项研究中，我们使用发芽酵母来鉴定重组以外的有助于减数分裂保真度的过程。我们发现，一种名为ZIP1的蛋白质介导了染色体着丝粒的配对，大大增加了它们在减数分裂中被正确分离的机会，从而防止了染色体数目错误的配子的形成。
In meiosis I, homologous chromosomes become paired and then separate from one another to opposite poles of the spindle. In humans, errors in this process are a leading cause of birth defects, mental retardation, and infertility. In most organisms, crossing-over, or exchange, between the homologous partners provides a link that promotes their proper, bipolar, attachment to the spindle. Attachment of both partners to the same pole can sometimes be corrected during a delay that is triggered by the spindle checkpoint. Studies of non-exchange chromosomes have shown that centromere pairing serves as an alternative to exchange by orienting the centromeres for proper microtubule attachment. Here, we demonstrate a new role for the synaptonemal complex protein Zip1. Zip1 localizes to the centromeres of non-exchange chromosomes in pachytene and mediates centromere pairing and segregation of the partners at meiosis I. Exchange chromosomes were also found to experience Zip1-dependent pairing at their centromeres. Zip1 was found to persist at centromeres, after synaptonemal complex disassembly, remaining there until microtubule attachment. Disruption of this centromere pairing, in spindle checkpoint mutants, randomized the segregation of exchange chromosomes. These results demonstrate that Zip1-mediated pairing of exchange chromosome centromeres promotes an initial, bipolar attachment of microtubules. This activity of Zip1 lessens the load on the spindle checkpoint, greatly reducing the chance that the cell will exit the checkpoint delay with an improperly oriented chromosome pair. Thus exchange, the spindle checkpoint, and centromere pairing are complementary mechanisms that ensure the proper segregation of homologous partners at meiosis I. Meiosis is a specialized cell division that halves the chromosome number and results in the production of gametes. In humans, meiosis normally produces gametes containing exactly one copy of each chromosome. Meiotic errors lead to gametes with incorrect chromosome numbers, a major cause of birth defects and infertility. A key step in meiosis (meiosis I) is the separation of homologous chromosomes. Homologous chromosomes first become physically linked by recombination, which keeps them together until they attach properly at their centromeres to the apparatus that will pull them to opposite sides of the cell. In this study we have used budding yeast to identify processes, beyond recombination, that contribute to meiotic fidelity. We have found that a protein, Zip1, mediates the pairing of chromosome centromeres in a way that greatly enhances the chance they will be properly separated in meiosis, thus preventing the formation of gametes with incorrect chromosome numbers.
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